Analysis of the arachidonyl-CoA synthetase ACSL4a as a potential regulator of BMP expression and of the role of BMPs in timing of cell commitment along the dorsoventral axis of the gastrulating zebrafish embryo [Elektronische Ressource] / vorgelegt von Björn Renisch

Analysis of the arachidonyl-CoA synthetase ACSL4a as a potential regulator of BMP expression and of the role of BMPs in timing of cell commitment along the dorsoventral axis of the gastrulating zebrafish embryo

- 9 - General introduction 2. General Introduction Higher animals develop from a fertilised egg to a three-dimensional, highly structured organismn consisting of multiple different cell types and tissues which - in the case of bilateria – are organized along at least two main body axes: the anterior-posterior (A-P) and the dorsal-ventral (D-V) axis. After fertilisation of the egg by a sperm cell, the first developmental process called cleavage is initiated, during which the zygote divides by several rounds of mitosis and (total or partial) cytokinesis into the so-called blastomeres. During these rapid cell divisions, the cell cycle just consists of an M- (mitosis) and an S- (DNA synthesis) phase, development is driven by maternally provided gene products, and cells become progressively smaller. However, once a certain ratio of DNA and cytoplasm is reached, G1 and G2 phases are established, cell divisions slow down, and zygotic transcription starts (mid-blastula-transition). After the blastula stages, the process of gastrulation starts, during which the three germlayers, ectoderm, mesoderm and endoderm, are formed. The ectoderm will later give rise to the epidermis, the nervous system and the neural crest, the mesoderm will form notochord, muscle, parts of the body skeleton, the blood, as well as vasculature and excretion tissues, and the endoderm will form the gastrointestinal system. In addition, the gastrulating embryo changes its overall shape and acquires a much more complex architecture, driven by the so-called morphogenetic cell movements during which mesoderm and endoderm become internalized. In addition, the body axes are set up and the general body plan is acquired. Gastrulation is followed by neurulation, during which the neural tube of the central nervous system is formed, and by organogenesis, during which the organs of the animal develop (Gilbert, 2003). All of these developmental processes are under the control of a complex system of signaling pathways and transcription factors. These factors act in a spatially and temporally strictly regulated and coordinated fashion. While some of them have redundant roles, others are absolutely indispensable, so that a single loss of their function would cause major changes in the embryonic body plan.

2.1. Early zebrafish development In 1981, George Steisinger introduced the zebrafish (Danio rerio) as a genetic model system for vertebrate development (Streisinger et al., 1981). The large number of progeny, the transparency of embryos and larvae, and the extracorporal development makes the zebrafish - 10 -